Tu1222 Non-Steroidal Anti-Inflammatory Drugs-Induced Small Intestinal Damage Is Associated With Autophagy and Apoptosis

Abstract

were decreased 1.5-fold (± 0.2, p<0.02) and 7.1-fold (± 1.4, p<0.01) in the setting of acute Hh inhibition. Finally, mice exposed to LDE treatment for 6 days were predisposed to significant, damaging colitis secondary to 3% DSS challenge as evidenced by increased weight loss (35% vs 15%), increased histological damage and inflammatory infiltrate when compared to solvent treated controls exposed to DSS. Our initial evaluation of the effect of Hh targeted therapies on the gastrointestinal tract indicates that inhibiting epithelial derived Hh signaling leads to a pro-inflammatory immune environment thereby predisposing the GI tract to inflammatory mediated damage when challenged. While targeting the Hh pathway for treatment of malignancies is attractive and powerful, understanding the resultant effect on mucosal immune homeostasis is a critical component to developing safe and tolerable therapies. 1 Sekulic et al NEJM 2012; 366:2171-79. 2 Chang et al. J. Am Acad Dermatol. 2013 Nov 1, S0190-9622 (13). 3 Keating GM Drugs 2012 72(11)1535-41.